The present invention relates generally to the prevention of diseases of cattle and, more specifically, to immunizing against such diseases by vaccination.
Bovine respiratory disease (BRD), bovine septicemia and bovine reproductive failure (BRF) result in great economic loss to the cattle industry. The primary bacterial pathogens implicated in BRD are Pasteurella haemolytica, P. multocida and Haemophilus somnus. H. somnus also causes bovine reproductive failure (BRF) and septicemia.
Current vaccines for H. somnus consist mainly of killed bacteria (bacterins) or bacterial extracts. Although there is evidence for protection in some controlled laboratory or animal challenge studies, efficacy in field studies is generally lacking. In some cases the vaccines cause such adverse side effects that their use is very limited. In other cases, little protection is seen. Thus, there is a need to develop improved vaccines to protect cattle from H. somnus mediated diseases. Such vaccines should contain key protective antigens that elicit appropriate antibody and cell-mediated immune responses. In addition, such vaccines should lack factors that cause adverse reactions and enable pathogens to evade immune recognition or effector mechanisms.
Accordingly, it is an object of the present invention to provide an effective and safe H. somnus vaccine for protection against BRD, BRF, septicemia and related disorders.
To accomplish these and other objectives, there has been provided, in accordance with one aspect of the present invention, a method for vaccinating cattle against diseases mediated by infection, comprising administering an effective amount of an H. somnus vaccine, wherein the H. somnus is susceptible to killing by bovine complement-containing serum.
According to another embodiment of the present invention, the H. somnus is live.
According to another embodiment of the present invention, the H. somnus is killed.
According to yet another embodiment of the present invention, the H. somnus lacks the expression of one or more immunoglobulin binding proteins present in virulent H. somnus. In a further embodiment, the lack of expression of one or more immunoglobulin binding proteins is achieved by the step of genetically engineering H. somnus to delete genes encoding the immunoglobulin binding proteins.
According to still yet another embodiment of the present invention, the H. somnus expresses a protective antigen. In a further embodiment, the protective antigen is a 40 kDa outermembrane protein.
According to another embodiment of the present invention, the H. somnus releases reduced amounts of endotoxin during growth as compared to virulent H. somnus. 
According to yet another embodiment of the present invention, the H. somnus is selected from the group consisting of PTA-600, PTA-601, PTA-602 and PTA-603, all on deposit with the American Type Culture Collection.
In accordance with another aspect of the present invention, a method is provided for vaccinating cattle against diseases mediated by infection, comprising administering an effective amount of an H. somnus vaccine, wherein the H. somnus releases reduced amounts of endotoxin as compared to virulent H. somnus. 
According to another embodiment of the present invention, the H. somnus is live.
According to another embodiment of the present invention, the H. somnus is killed.
According to yet another embodiment of the present invention, the H. somnus is sensitive to killing by complement-containing bovine serum.
According to still yet another embodiment of the present invention, the H. somnus lacks the expression of one or more immunoglobulin binding proteins present in virulent H. somnus. In a further embodiment, the lack of expression of one or more immunoglobulin binding proteins is achieved by the step of genetically engineering H. somnus to delete genes encoding the immunoglobulin binding proteins.
According to another embodiment of the present invention, the H. somnus expresses a protective antigen. In a further embodiment, the protective antigen is a 40 kDa outermembrane protein.
According to yet another embodiment of the present invention, the H. somnus is selected from the group consisting of PTA-600, PTA-601, PTA-602 and PTA-603, all on deposit with the American Type Culture Collection.
In further embodiments of the present invention, the vaccines described above use an H. somnus genetically engineered to express one or more protective antigens. In further embodiments, the protective antigens are from bacterial pathogens other than H. somnus. 
Other objects, features and advantages of the present invention will become apparent from the following detailed description.